Active Surveillance und die moderne Diagnostik des Prostatatkarzinoms

Zusammenfassung

Hintergrund

Ein Teil der Prostatakarzinome wird in der primären Prostatabiopsie nicht detektiert, sodass bei weiterbestehendem Verdacht eine erneute Biopsie erfolgen muss. Neben der Problematik der Falsch-negativ-Rate in der systematischen Biopsie, besteht eine hohe Missklassifikationsrate, insbesondere das Tumorgrading betreffend. Dadurch kann es zu einer verspäteten Diagnose aggressiverer Tumoreigenschaften und im ungünstigsten Falle zu einem Versäumnis kurativer Ansätze kommen. Aufgrund dieser Problematik bestehen zahlreiche Ansätze, die Therapieentscheidung und Überwachung durch den Einsatz moderner Bildgebung und genetischer Biomarker zu optimieren

Ziel

Der Beitrag vermittelt eine Übersicht über die Active-Surveillance(AS)-Definitionen, die Problematik der Prostatakarzinomdetektion und genaue Grading-Abschätzung in der systematischen transrektalen Biopsie und den Einsatz der multiparametrischen MRT (mpMRT), der gezielten MRT- Fusionsbiopsie und genetischer Biomarker als potenzielle Lösungsansätze sowie deren Integration im klinischen Alltag.

Material und Methoden

Aktuelle Literatur wurde recherchiert und im Kontext mit eigenen Erfahrungen ausgewertet.

Ergebnisse

Die mpMRT sowie die gezielte MRT-Fusionsbiopsie sind dem aktuellen Standard der systematischen Biopsie in der Detektion des klinisch signifikanten Prostatakarzinoms überlegen. Besonders deutlich zeigt sich dies im Falle der Wiederholungsbiopsie des anterioren Prostatakarzinoms, einer persistierend suspekten PSA-Dynamik und Einschluss und Monitoring von AS-Patienten. Auch die Kombination mit weiteren neuartigen Prädiktoren sind weitere vielversprechende Ansätze.

Schlussfolgerung

Der potenzielle diagnostische Mehrwert kann ausschließlich durch eine interdisziplinäre Verknüpfung der zunehmend komplexeren diagnostischen Schritte erreicht werden. Effektive Lösungen im Rahmen der interdisziplinären Zusammenarbeit von Radiologen und Urologen auf Niveau der Fachgesellschaften sind notwendig, um Fragen bezüglich des Zeitaufwands und der Ressourcenverteilung mit den Leistungserstattern zu adressieren.

https://ift.tt/2Tethe7

CRISPR/Cas9 Editing of Glia Maturation Factor Regulates Mitochondrial Dynamics by Attenuation of the NRF2/HO-1 Dependent Ferritin Activation in Glial Cells

Abstract

Microglial cells are brain specific professional phagocytic immune cells that play a crucial role in the inflammation- mediated neurodegeneration especially in Parkinson's disease (PD) and Alzheimer's disease. Glia maturation factor (GMF) is a neuroinflammatory protein abundantly expressed in the brain. We have previously shown that GMF expression is significantly upregulated in the substantia nigra (SN) of PD brains. However, its possible role in PD progression is still not fully understood. The Clustered-Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR Associated (Cas) protein9 (CRISPR/Cas9) system is a simple, rapid and often extremely efficient gene editing tool at desired loci, enabling complete gene knockout or homology directed repair. In this study, we examined the effect of GMF editing by using the CRISPR/Cas9 technique in BV2 microglial cells (hereafter referred to as BV2-G) on oxidative stress and nuclear factor erythroid 2-related factor 2 (NRF2)/Hemeoxygenase1 (HO-1)-dependent ferritin activation after treatment with (1-methyl-4-phenylpyridinium) MPP⁺. Knockout of GMF in BV2-G cells significantly attenuated oxidative stress via reduced ROS production and calcium flux. Furthermore, deficiency of GMF significantly reduced nuclear translocation of NRF2, which modulates HO-1 and ferritin activation, cyclooxygenase 2 (COX2) and nitric oxide synthase 2 (NOS2) expression in BV2 microglial cells. Lack of GMF significantly improved CD11b and CD68 positive microglial cells as compared with untreated cells. Our results also suggest that pharmacological and genetic intervention targeting GMF may represent a promising and a novel therapeutic strategy in controlling Parkinsonism by regulating microglial functions. Targeted regulation of GMF possibly mediates protein aggregation in microglial homeostasis associated with PD progression through regulation of iron metabolism by modulating NRF2-HO1 and ferritin expression.

https://ift.tt/2U9YiNB

Tattoo Removal as a Resettlement Service to Reduce Incarceration Among Mexican Migrants

Abstract

In Mexico, tattooed migrants face discrimination and are at high-risk of incarceration, thus, we assessed whether receiving laser tattoo removal affected the likelihood of incarceration. In 2015–2016, 89 adults ages ≥ 18 years with visible tattoos were recruited at a free-clinic to receive laser tattoo removal or assigned to the wait-list; all completed baseline and 6-month questionnaires. Overall, 97.8% of participants ever migrated to the USA. In multivariate analyses restricted to migrants (n = 87), those receiving laser tattoo removal [Adjusted Odds Ratio (AOR) 0.27, 95% CI 0.07–0.89] and possessing a Mexican Voting card (AOR 0.14; 95% CI 0.03–0.58) were significantly less likely than wait-list participants to be incarcerated at 6-months. Previously incarcerated participants were significantly more likely to be incarcerated at follow-up. Tattoo removal may reduce incarceration among Mexican migrants. Future studies can assess other health and social benefits of tattoo removal for migrants/deportees returning to Mexico.

https://ift.tt/2EdzgGq

The identification and treatment of intestinal malrotation in older children

Abstract

Purpose

Intestinal malrotation is often diagnosed in infancy. The true incidence of malrotation outside of this age is unknown. These patients can present atypically or be asymptomatic and diagnosed incidentally. We evaluate the incidence, clinical presentation, ideal imaging, and intra-operative findings of patients with malrotation over 1 year of age.

Methods

Retrospective review was conducted in patients older than 1 year, treated for malrotation at a single pediatric tertiary care center from 2000 to 2015. Data analyzed included demographics, presentation, imaging, intraoperative findings, and follow-up. Patients predisposed to malrotation were excluded.

Results

246 patients were diagnosed with malrotation, of which 77 patients were older than 1 year of age. The most common presenting symptoms were vomiting (68%) and abdominal pain (57%). The most common method of diagnosis was UGI (61%). In 88%, the UGI revealed malrotation. 73 of 75 were confirmed to have malrotation at surgery. Intra-operatively, 60% were found to have a malrotated intestinal orientation and 33% with a non-rotated orientation. Obstruction was present in 22% with 12% having volvulus. Of those with follow-up, 58% reported alleviation of symptoms.

Conclusion

Despite age malrotation should be on the differential given a variable clinical presentation. UGI should be conducted to allow for prompt diagnosis and surgical intervention.

https://ift.tt/2IAKCJR

Rare Diseases Day and Brain Awareness Week: the active participation of Neurological Sciences

https://ift.tt/2SwIeE1

Evaluation of treatment adherence in patients with Behçet’s disease: its relation to disease manifestations, patients’ beliefs about medications, and quality of life

Abstract

Introduction/objectives

Despite its importance, adherence to treatment has not been sufficiently studied in Behçet's disease (BD). The aim of this study was to evaluate medication adherence in BD using the Compliance Questionnaire of Rheumatology (CQR) and factors potentially affecting it.

Method

This cross-sectional study included 67 consecutive BD patients including 57 (85%) males with a mean age of 35.1 ± 9.27 years and mean disease duration of 129 ± 91 months. The cumulative clinical manifestations, the Behçet's Disease Current Activity Form (BDCAF) score, and the Vasculitis Damage Index (VDI) were recorded. The CQR, Socioeconomic Status Questionnaire for Health Research in Egypt (SES), the Beliefs about Medication Questionnaire (BMQ), and the Short Form 36 (SF-36) quality of life assessment questionnaire were administered to the patients. Linear regression analysis was done to determine independent predictors of CQR.

Results

The mean BDCAF score was 3.27 ± 3.54 and the VDI was 3.36 ± 2.21. The mean CQR score was 69.2 ± 11.79. The CQR score varied significantly among different health sources (p = 0.02), with no relationship detected with other sociodemographic characteristics, nor with clinical characteristics or the SF-36. Among the investigated medications' complexities, severity of side effects showed significantly different CQR scores (p = 0.004), and a weak positive correlation between medications' numbers and the CQR was detected. Predictors for higher CQR scores included the necessity beliefs score of the BMQ (β = 1.1, p < 0.001); whereas, predictors for lower CQR scores were the harm and concern BMQ subscales ((β = − 1.5, p = 0.004) and (β = − 0.72, p = 0.032), respectively).

Conclusions

Beliefs about medications were the only predictor for adherence in our cohort.

https://ift.tt/2ExVlAL

Dysregulation of the Wnt signaling pathway in South African patients with diffuse systemic sclerosis

Abstract

The objective was to explore changes in gene expression in Wnt pathway genes in skin samples of black South Africans with diffuse cutaneous systemic sclerosis (dcSSc). Affected (forearm) and unaffected (upper back) skin samples of eight Black South Africans with active early dcSSc were compared to skin samples from seven ethnically matched control subjects. The Wnt Pathway Plus RT² Profiler qPCR Array was used to determine gene expression and analyzed for differential expression between cases and controls. Selective validation was done using single-gene TaqMan assays. Several genes were similarly upregulated in both affected and unaffected skin of the dcSSc patients compared to controls. These included the Wnt ligands WNT7A and WNT10A, the frizzled receptors FZD8 and FZD9, intracellular signaling proteins AXIN1 and AXIN2, and the pathway target genes FGF4 and MMP7. Principal component analysis revealed patients clustering into two groups, which co-segregated with clinical features of interstitial lung disease and/or inflammatory myopathy, or the absence of an inflammation phenotype. These two groups showed paradoxical gene expression of the genes TCF7, SOX17, and FRZB in affected and unaffected skin. This study provides further evidence of dysregulation of gene expression at various levels of the Wnt signaling pathway in dcSSc. Moreover, principal component analysis showed two distinct patient clusters of gene expression, which co-segregated with the presence or absence of clinical inflammatory features, and may reflect different pathological pathways in dcSSc.

https://ift.tt/2Vo6YQu

First-degree relatives of axial spondyloarthritis patients of the pre-SpA cohort would consider using medication in a preventive setting

Abstract

To study the willingness of first-degree relatives of axial spondyloarthritis (axSpA) patients to use preventive medication. First-degree relatives of HLA-B27-positive axSpA patients (pre-SpA cohort) (n = 106) completed a survey including scenarios varying in disease risk, side effects, and treatment effect of hypothetical preventive medication and questions about their perceived risk of developing SpA and assessment of the severity of SpA. The willingness to use preventive medication was 63.2–91.5% (with 30–70% SpA risk, respectively) and declined to 27.4–51.9% respectively, when side effects might occur. On a visual analogue scale (VAS) 0–100 mm (totally disagree-totally agree) (median;range), participants were not occupied by the thought of developing SpA (23;13–39), did not assume that they will eventually develop SpA (22;14–35), and consider SpA a severe disease (66;52–78). The willingness to use preventive medication was negatively influenced by their own risk assessment of developing SpA (OR = 1.17, p = .001) and was not primarily influenced by costs and route of administration. First-degree relatives of axSpA patients with a clearly increased disease risk (70%) would largely consider using preventive medication. Their willingness roughly halved by the possible occurrence of side effects. Participants' perceived risk to develop SpA and their assessment of the severity of SpA negatively influenced the willingness to use preventive medication.

https://ift.tt/2EAupk0

The association of CD40 polymorphism (rs1883832C/T) and soluble CD40 with the risk of systemic lupus erythematosus among Egyptian patients

Abstract

Background

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Considerable evidence supports a genetic basis for susceptibility to SLE. Genetic and functional data suggested the CD40 receptor (CD40) and CD40 ligand (CD40L) as strong candidate genes for SLE.

Aim

To investigate whether CD40 gene rs1883832 C/T single-nucleotide polymorphism (SNP) and/or soluble CD40 (sCD40) are associated with SLE in the Egyptian population.

Subjects and methods

The study included a hundred SLE patients, and a fifty age- and gender-matched healthy control subjects. CD40 gene rs1883832 C/T genotyping was carried out using restriction fragment length polymorphism (RFLP), while sCD40 levels were measured by ELISA.

Results

CD40 rs1883832C/T genotypes (CC, TT, and CT) as well as CD40 alleles (C and T) did not differ between SLE patients and normal control (p = 0.63, 0.37, and 0.31 respectively). Though did not reach statistical significance, carriers of genotype CT had 1.5 times more chance to develop SLE compared to wild homozygous CC genotype carriers (OR 1.44), while carriers of genotype TT had ~ 2 times more chance to have SLE than CC carries (OR 1.96). Accordingly, the carriers of the T allele had ¬ 1.5 times more chance to get SLE compared to the carriers of the C allele (OR 1.4). The serum sCD40 level was significantly higher in SLE patients compared to healthy control (3.4 vs. 0.8 ng/mL, p < 0.001). In SLE patients, using CC as the reference genotype, serum sCD40 level was significantly higher in the carriers of the homozygous genotype TT (3.8 ± 1.3 vs. 2.9 ± 1.9, p = 0.0001), and T allele (3.6 ± 1.4 vs. 3.0 ± 1.5, p = 0.003). Moreover, sCD40 could discriminate SLE patients from normal subjects at a cutoff value of 0.885 ng/mL with 98% sensitivity and 96% specificity (AUC = 0.999, p < 0.001).

Conclusions

The study did not prove CD40 gene (rs1883832 C/T) polymorphism as a clear risk factor of SLE in this cohort of Egyptian patients, though it was highly likely associated with the carriers of T allele. In the same context, significant high sCD40 levels were observed in the T allele carriers.

https://ift.tt/2Vo6REy

The Isolation and Characterization of Kronos, a Novel Caulobacter Rhizosphere Phage that is Similar to Lambdoid Phages

Abstract

Despite their ubiquity, relatively few bacteriophages have been characterized. Here, we set out to explore Caulobacter bacteriophages (caulophages) in the rhizosphere and characterized Kronos, the first caulophage isolated from the rhizosphere. Kronos is a member of the Siphoviridae family since it has a long flexible tail. In addition, an analysis of the Kronos genome indicated that many of the predicted proteins were distantly related to those of bacteriophages in the lambdoid family. Consistent with this observation, we were able to demonstrate the presence of cos sites that are similar to those found at the ends of lambdoid phage genomes. Moreover, Kronos displayed a relatively rare head and tail morphology compared to other caulophages but was similar to that of the lambdoid phages. Taken together, these data indicate that Kronos is distantly related to lambdoid phages and may represent a new Siphoviridae genus.

https://ift.tt/2BWVT1o

Highlights of the Issue 3, 2019

https://ift.tt/2tFxj0M

Biomarkers of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease

Abstract

Background

Currently, there are no reliable indicators for predicting intravenous immunoglobulin resistance and coronary artery lesions in the early stage of Kawasaki disease.

Methods

A total of 300 patients with Kawasaki disease were studied retrospectively. Laboratory data were compared between the intravenous immunoglobulin resistant (29 patients) and responsive groups, and between the groups with coronary artery lesions (48 patients) and without coronary artery lesions.

Results

The intravenous immunoglobulin resistant group had significantly higher D-dimer, globulin, interleukin-6 and serum ferritin levels in comparison to the intravenous immunoglobulin responder group. D-dimer level had a sensitivity of 87.0% and a specificity of 56.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 1.09 mg/L. Globulin had a sensitivity of 62.1% and a specificity of 82.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 34.7 g/L. Serum ferritin level had a sensitivity of 42.9% and a specificity of 88.8% for predicting intravenous immunoglobulin resistance at a cutoff point of 269.7 ng/mL. The patients with coronary artery lesions had higher D-dimer and tumor necrosis factor-α level. D-dimer level had a sensitivity of 50% and a specificity of 78.6% for predicting coronary artery lesions at a cutoff point of 1.84 mg/L. Based on analysis by multivariate logistic regression, serum ferritin and globulin were independent risks for intravenous immunoglobulin resistance, D-dimer was independent risk for coronary artery lesions.

Conclusions

Elevated serum ferritin, globulin and D-dimer levels are significantly associated with intravenous immunoglobulin resistance in Kawasaki disease. Moreover, serum D-dimer is significantly increased in Kawasaki disease with coronary artery lesions.

https://ift.tt/2EfXJuI

Clinical Perspectives in Upper Limb Prostheses: An Update

Abstract

Purpose of Review

This paper aims to summarise the development trends in upper limb bionics over the past 5 years.

Recent Findings

Increasingly pattern recognition and regression control algorithms are being used to decode EMG signals for prosthetic control and are moving towards clinically available devices. Additionally, bionic reconstruction has built on the principles of targeted muscle reinnervation to add another rung to the reconstructive ladder for upper limb deficits. Finally, novel methods to provide sensation to prostheses are trialled not just in the laboratory but in home testing systems as well.

Summary

Engineering, surgical and rehabilitation methods are gradually adding more capabilities to modern prostheses, moving towards the goal of replicating natural hand function.

https://ift.tt/2EqBiDp

Intravenous lidocaine infusion as a component of multimodal analgesia for colorectal surgery—measurement of plasma levels

Abstract

Background

Growing evidence suggests that intravenous lidocaine as a component of multimodal analgesia improves recovery after major colorectal surgery. There is little published data regarding ideal dosing and target plasma concentration in this context, and we wanted to establish our dosing schedule was safe by measuring blood levels of lidocaine.

Methods

We measured the plasma lidocaine concentration of 32 patients at 30 min, 6 h and 12 h after starting intravenous lidocaine infusion for analgesia after major colorectal surgery. Patients received a bolus of 1.5 mg kg⁻¹ over 20 min at the time of induction of anaesthesia. This was followed by a continuous infusion of 2% w/v lidocaine at 3 ml hr⁻¹ (60 mg hr⁻¹) for patients weighing up to 70 kg and 6 ml hr⁻¹ (120 mg hr⁻¹) for patients weighing over 70 kg, using actual body weight.

Results

The overall mean plasma lidocaine concentration was 4.0 μg ml⁻¹ (range 0.6–12.3 μg ml⁻¹). In patients treated with the higher infusion dose, the mean concentration was 4.6 μg ml⁻¹ compared to 3.2 μg ml⁻¹ in those patients on the lower dose. Mean levels were higher at 6 h than 30 min and higher again at 12 h. There were no adverse events or reports of symptoms of local anaesthetic toxicity.

Conclusions

Whilst there were no signs or symptoms of lidocaine toxicity in our patients, there was a wide range of plasma concentrations including some over 10 μg ml⁻¹; a level above which symptoms of toxicity may be expected. We have changed our dosing protocol to using ideal rather than actual body weight based on these results.

https://ift.tt/2EylfEu

Investigating the effect of proteoglycan 4 on hyaluronan solution properties using confocal fluorescence recovery after photobleaching

Abstract

Background

The objective of this study was to use confocal fluorescence recovery after photobleaching (FRAP) to examine the specific and dose-dependent effect of proteoglycan 4 (PRG4) on hyaluronan (HA) solutions of different molecular weight; and assess the effect of reduction and alkylation (R/A) of PRG4 on its effects on HA solutions.

Methods

Confocal FRAP was used to determine the diffusion coefficient of fluorescein isothiocyanate (FITC)-dextran tracer (D_t) through 1500 kDa and 500 kDa HA solutions (0–3.3 mg/ml) ± PRG4 or a control protein, bovine serum albumin (BSA), at physiological (450 μg/ml) or pathophysiological (45 μg/ml) concentrations. The effect of PRG4 or R/A PRG4 on 1500 kDa HA solutions was also investigated. Empirical constants obtained from fitting data to the universal scaling equation were used to calculate the average distribution of apparent mesh sizes.

Results

PRG4 at both 45 and 450 μg/ml slowed the diffusion of the FITC-dextran tracer for all concentrations of HA and caused a decrease in the apparent mesh size within the HA solution. This effect was specific to PRG4, not observed with BSA, but not dependent on its tertiary/quaternary structure as the effect remained after R/A of PRG4.

Conclusions

These results demonstrate that PRG4 can significantly alter the solution properties of HA; PRG4 essentially reduced the permeability of the HA network. This effect may be due to PRG4 entangling HA molecules through binding and/or HA crowding PRG4 molecules into a self-assembled network. Collectively these findings contribute to the understanding of PRG4 and HA interaction(s) in solution and therefore the function of SF in diarthroidal joints.

https://ift.tt/2NCA4cp

A Longitudinal Analysis of Pressurized Wideband Absorbance Measures in Healthy Young Infants

Objectives: Wideband absorbance (WBA) is an emerging technology to evaluate the conductive pathway (outer and middle ear) in young infants. While a wealth of research has been devoted to measuring WBA at ambient pressure, few studies have investigated the use of pressurized WBA with this population. The purpose of this study was to investigate the effect of age on WBA measured under pressurized conditions in healthy infants from 0 to 6 months of age. Design: Forty-four full-term healthy neonates (17 males and 27 females) participated in a longitudinal study. The neonates were assessed at 1-month intervals from 0 to 6 months of age using high-frequency tympanometry, acoustic stapedial reflex, distortion product otoacoustic emissions, and pressurized WBA. The values of WBA at tympanometric peak pressure (TPP) and 0 daPa across the frequencies from 0.25 to 8 kHz were analyzed as a function of age. Results: A linear mixed model analysis, applied to the data, revealed significantly different WBA patterns among the age groups. In general, WBA measured at TPP and 0 daPa decreased at low frequencies (

from #Audiology via ola Kala on Inoreader https://ift.tt/2ICMz8F
via IFTTT

Benefit of Higher Maximum Force Output on Listening Effort in Bone-Anchored Hearing System Users: A Pupillometry Study

Objectives: The aim of this study was to compare listening effort, as estimated via pupillary response, during a speech-in-noise test in bone-anchored hearing system (BAHS) users wearing three different sound processors. The three processors, Ponto Pro (PP), Ponto 3 (P3), and Ponto 3 SuperPower (P3SP), differ in terms of maximum force output (MFO) and MFO algorithm. The hypothesis was that listeners would allocate lower listening effort with the P3SP than with the PP, as a consequence of a higher MFO and, hence, fewer saturation artifacts in the signal. Design: Pupil dilations were recorded in 21 BAHS users with a conductive or mixed hearing loss, during a speech-in-noise test performed at positive signal-to-noise ratios (SNRs), where the speech and noise levels were individually adjusted to lead to 95% correct intelligibility with the PP. The listeners had to listen to a sentence in noise, retain it for 3 seconds and then repeat it, while an eye-tracking camera recorded their pupil dilation. The three sound processors were tested in random order with a single-blinded experimental design. Two conditions were performed at the same SNR: Condition 1, where the speech level was designed to saturate the PP but not the P3SP, and condition 2, where the overall sound level was decreased relative to condition 1 to reduce saturation artifacts. Results: The P3SP led to higher speech intelligibility than the PP in both conditions, while the performance with the P3 did not differ from the performance with the PP and the P3SP. Pupil dilations were analyzed in terms of both peak pupil dilation (PPD) and overall pupil dilation via growth curve analysis (GCA). In condition 1, a significantly lower PPD, indicating a decrease in listening effort, was obtained with the P3SP relative to the PP. The PPD obtained with the P3 did not differ from the PPD obtained with the other two sound processors. In condition 2, no difference in PPD was observed across the three processors. The GCA revealed that the overall pupil dilation was significantly lower, in both conditions, with both the P3SP and the P3 relative to the PP, and, in condition 1, also with the P3SP relative to the P3. Conclusions: The overall effort to process a moderate to loud speech signal was significantly reduced by using a sound processor with a higher MFO (P3SP and P3), as a consequence of fewer saturation artifacts. These findings suggest that sound processors with a higher MFO may help BAHS users in their everyday listening scenarios, in particular in noisy environments, by improving sound quality and, thus, decreasing the amount of cognitive resources utilized to process incoming speech sounds. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal’s Web site (www.ear-hearing.com). ACKNOWLEDGMENTS: The authors thank Matthew Winn for the helpful discussion of the results. This work was supported by Oticon Medical AB (Askim, Sweden). T. R., M. H., T. L., D. W., C. W., and P. M. designed the experiments; C. W. performed the experiments; F. B. and D. W. analyzed the data; F. B. wrote the article and provided the Supplementary Digital Content; all authors discussed the results and provided critical revision on the manuscript. The authors have no conflicts of interest to disclose. Received August 3, 2018; accepted December 18, 2018. Address for correspondence: Federica Bianchi, Oticon Medical AB, Kongebakken 9, Smørum, Denmark. E-mail: fedb@oticonmedical.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader https://ift.tt/2Te1mej
via IFTTT

A Comparison of Electrical Stimulation Levels Across Ears for Children With Sequential Bilateral Cochlear Implants

Objectives: To compare threshold and comfortable levels between a first and second cochlear implant (CI) for children, and to consider if the degree of difference between CIs was related to the age at bilateral implantation or the time between implants. A secondary objective was to examine the changes in levels over time for each CI . Design: Fifty-seven participants were selected from the 146 children and young adults who received a first Nucleus CI as a child, and received a second implant at the Royal Victorian Eye and Ear Hospital between September 2003 and December 2011. Exclusion criteria included an older implant type, incomplete array insertion, incomplete data available, and a pulse width higher than the default. Using measurements from clinical sessions, the threshold levels, comfortable levels, and dynamic range of electrical stimulation were compared at three electrode array regions and at the “initial” (first 10 weeks), 2-year, and 5-year postoperative time points. The T-ratio and C-ratio for each array region and each time point were calculated by dividing each mean (n = 3 electrodes) level for the second implant by that for the first implant. Results: The T-ratio was generally not significantly different to one, indicating no differences in threshold levels between the second and first implants; however, threshold levels were lower for the second implant in the apical region at the initial time point, and there was a significant difference in threshold levels in the apical region for children with a Contour Advance array for the second implant and an older-style array (i.e., Contour) for the first implant. For each implant individually, there were no significant changes in threshold levels across time. The C-ratio was significantly

from #Audiology via ola Kala on Inoreader https://ift.tt/2IEbDwi
via IFTTT

Different Associations between Auditory Function and Cognition Depending on Type of Auditory Function and Type of Cognition

Objectives: Previous studies strongly suggest that declines in auditory threshold can lead to impaired cognition. The aim of this study was to expand that picture by investigating how the relationships between age, auditory function, and cognitive function vary with the types of auditory and cognitive function considered. Design: Three auditory constructs (threshold, temporal-order identification, and gap detection) were modeled to have an effect on four cognitive constructs (episodic long-term memory, semantic long-term memory, working memory, and cognitive processing speed) together with age that could have an effect on both cognitive and auditory constructs. The model was evaluated with structural equation modeling of the data from 213 adults ranging in age from 18 to 86 years. Results: The model provided good a fit to the data. Regarding the auditory measures, temporal-order identification had the strongest effect on the cognitive functions, followed by weaker indirect effects for gap detection and nonsignificant effects for threshold. Regarding the cognitive measures, the association with audition was strongest for semantic long-term memory and working memory but weaker for episodic long-term memory and cognitive speed. Age had a very strong effect on threshold and cognitive speed, a moderate effect on temporal-order identification, episodic long-term memory, and working memory, a weak effect on gap detection, and nonsignificant, close to zero effect on semantic long-term memory. Conclusions: The result shows that auditory temporal-order function has the strongest effect on cognition, which has implications both for which auditory concepts to include in cognitive hearing science experiments and for practitioners. The fact that the total effect of age was different for different aspects of cognition and partly mediated via auditory concepts is also discussed. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal’s Web site (www.ear-hearing.com). ACKNOWLEDGMENTS: This study was financed by an excellence grant [349-2007-8654] from the Swedish Research council; a grant [2012-1693] from The Swedish Research Council for Health, Working Life and Welfare (to J.R.) and a grant [R01 AG008293] from the National Institute on Aging (to L.H.). The authors have no conflicts of interest to disclose. Address for correspondence: Henrik Danielsson, Department of Behavioural Sciences and Learning, Linköping University, 581 83 Linköping, Sweden. Email: henrik.danielsson@liu.se Received December 14, 2016; accepted December 18, 2018. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader https://ift.tt/2Tm8YeA
via IFTTT

A Longitudinal Analysis of Pressurized Wideband Absorbance Measures in Healthy Young Infants

Objectives: Wideband absorbance (WBA) is an emerging technology to evaluate the conductive pathway (outer and middle ear) in young infants. While a wealth of research has been devoted to measuring WBA at ambient pressure, few studies have investigated the use of pressurized WBA with this population. The purpose of this study was to investigate the effect of age on WBA measured under pressurized conditions in healthy infants from 0 to 6 months of age. Design: Forty-four full-term healthy neonates (17 males and 27 females) participated in a longitudinal study. The neonates were assessed at 1-month intervals from 0 to 6 months of age using high-frequency tympanometry, acoustic stapedial reflex, distortion product otoacoustic emissions, and pressurized WBA. The values of WBA at tympanometric peak pressure (TPP) and 0 daPa across the frequencies from 0.25 to 8 kHz were analyzed as a function of age. Results: A linear mixed model analysis, applied to the data, revealed significantly different WBA patterns among the age groups. In general, WBA measured at TPP and 0 daPa decreased at low frequencies (

from #Audiology via ola Kala on Inoreader https://ift.tt/2ICMz8F
via IFTTT

Benefit of Higher Maximum Force Output on Listening Effort in Bone-Anchored Hearing System Users: A Pupillometry Study

Objectives: The aim of this study was to compare listening effort, as estimated via pupillary response, during a speech-in-noise test in bone-anchored hearing system (BAHS) users wearing three different sound processors. The three processors, Ponto Pro (PP), Ponto 3 (P3), and Ponto 3 SuperPower (P3SP), differ in terms of maximum force output (MFO) and MFO algorithm. The hypothesis was that listeners would allocate lower listening effort with the P3SP than with the PP, as a consequence of a higher MFO and, hence, fewer saturation artifacts in the signal. Design: Pupil dilations were recorded in 21 BAHS users with a conductive or mixed hearing loss, during a speech-in-noise test performed at positive signal-to-noise ratios (SNRs), where the speech and noise levels were individually adjusted to lead to 95% correct intelligibility with the PP. The listeners had to listen to a sentence in noise, retain it for 3 seconds and then repeat it, while an eye-tracking camera recorded their pupil dilation. The three sound processors were tested in random order with a single-blinded experimental design. Two conditions were performed at the same SNR: Condition 1, where the speech level was designed to saturate the PP but not the P3SP, and condition 2, where the overall sound level was decreased relative to condition 1 to reduce saturation artifacts. Results: The P3SP led to higher speech intelligibility than the PP in both conditions, while the performance with the P3 did not differ from the performance with the PP and the P3SP. Pupil dilations were analyzed in terms of both peak pupil dilation (PPD) and overall pupil dilation via growth curve analysis (GCA). In condition 1, a significantly lower PPD, indicating a decrease in listening effort, was obtained with the P3SP relative to the PP. The PPD obtained with the P3 did not differ from the PPD obtained with the other two sound processors. In condition 2, no difference in PPD was observed across the three processors. The GCA revealed that the overall pupil dilation was significantly lower, in both conditions, with both the P3SP and the P3 relative to the PP, and, in condition 1, also with the P3SP relative to the P3. Conclusions: The overall effort to process a moderate to loud speech signal was significantly reduced by using a sound processor with a higher MFO (P3SP and P3), as a consequence of fewer saturation artifacts. These findings suggest that sound processors with a higher MFO may help BAHS users in their everyday listening scenarios, in particular in noisy environments, by improving sound quality and, thus, decreasing the amount of cognitive resources utilized to process incoming speech sounds. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal’s Web site (www.ear-hearing.com). ACKNOWLEDGMENTS: The authors thank Matthew Winn for the helpful discussion of the results. This work was supported by Oticon Medical AB (Askim, Sweden). T. R., M. H., T. L., D. W., C. W., and P. M. designed the experiments; C. W. performed the experiments; F. B. and D. W. analyzed the data; F. B. wrote the article and provided the Supplementary Digital Content; all authors discussed the results and provided critical revision on the manuscript. The authors have no conflicts of interest to disclose. Received August 3, 2018; accepted December 18, 2018. Address for correspondence: Federica Bianchi, Oticon Medical AB, Kongebakken 9, Smørum, Denmark. E-mail: fedb@oticonmedical.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader https://ift.tt/2Te1mej
via IFTTT

A Comparison of Electrical Stimulation Levels Across Ears for Children With Sequential Bilateral Cochlear Implants

Objectives: To compare threshold and comfortable levels between a first and second cochlear implant (CI) for children, and to consider if the degree of difference between CIs was related to the age at bilateral implantation or the time between implants. A secondary objective was to examine the changes in levels over time for each CI . Design: Fifty-seven participants were selected from the 146 children and young adults who received a first Nucleus CI as a child, and received a second implant at the Royal Victorian Eye and Ear Hospital between September 2003 and December 2011. Exclusion criteria included an older implant type, incomplete array insertion, incomplete data available, and a pulse width higher than the default. Using measurements from clinical sessions, the threshold levels, comfortable levels, and dynamic range of electrical stimulation were compared at three electrode array regions and at the “initial” (first 10 weeks), 2-year, and 5-year postoperative time points. The T-ratio and C-ratio for each array region and each time point were calculated by dividing each mean (n = 3 electrodes) level for the second implant by that for the first implant. Results: The T-ratio was generally not significantly different to one, indicating no differences in threshold levels between the second and first implants; however, threshold levels were lower for the second implant in the apical region at the initial time point, and there was a significant difference in threshold levels in the apical region for children with a Contour Advance array for the second implant and an older-style array (i.e., Contour) for the first implant. For each implant individually, there were no significant changes in threshold levels across time. The C-ratio was significantly

from #Audiology via ola Kala on Inoreader https://ift.tt/2IEbDwi
via IFTTT

Different Associations between Auditory Function and Cognition Depending on Type of Auditory Function and Type of Cognition

Objectives: Previous studies strongly suggest that declines in auditory threshold can lead to impaired cognition. The aim of this study was to expand that picture by investigating how the relationships between age, auditory function, and cognitive function vary with the types of auditory and cognitive function considered. Design: Three auditory constructs (threshold, temporal-order identification, and gap detection) were modeled to have an effect on four cognitive constructs (episodic long-term memory, semantic long-term memory, working memory, and cognitive processing speed) together with age that could have an effect on both cognitive and auditory constructs. The model was evaluated with structural equation modeling of the data from 213 adults ranging in age from 18 to 86 years. Results: The model provided good a fit to the data. Regarding the auditory measures, temporal-order identification had the strongest effect on the cognitive functions, followed by weaker indirect effects for gap detection and nonsignificant effects for threshold. Regarding the cognitive measures, the association with audition was strongest for semantic long-term memory and working memory but weaker for episodic long-term memory and cognitive speed. Age had a very strong effect on threshold and cognitive speed, a moderate effect on temporal-order identification, episodic long-term memory, and working memory, a weak effect on gap detection, and nonsignificant, close to zero effect on semantic long-term memory. Conclusions: The result shows that auditory temporal-order function has the strongest effect on cognition, which has implications both for which auditory concepts to include in cognitive hearing science experiments and for practitioners. The fact that the total effect of age was different for different aspects of cognition and partly mediated via auditory concepts is also discussed. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal’s Web site (www.ear-hearing.com). ACKNOWLEDGMENTS: This study was financed by an excellence grant [349-2007-8654] from the Swedish Research council; a grant [2012-1693] from The Swedish Research Council for Health, Working Life and Welfare (to J.R.) and a grant [R01 AG008293] from the National Institute on Aging (to L.H.). The authors have no conflicts of interest to disclose. Address for correspondence: Henrik Danielsson, Department of Behavioural Sciences and Learning, Linköping University, 581 83 Linköping, Sweden. Email: henrik.danielsson@liu.se Received December 14, 2016; accepted December 18, 2018. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader https://ift.tt/2Tm8YeA
via IFTTT

A Longitudinal Analysis of Pressurized Wideband Absorbance Measures in Healthy Young Infants

Objectives: Wideband absorbance (WBA) is an emerging technology to evaluate the conductive pathway (outer and middle ear) in young infants. While a wealth of research has been devoted to measuring WBA at ambient pressure, few studies have investigated the use of pressurized WBA with this population. The purpose of this study was to investigate the effect of age on WBA measured under pressurized conditions in healthy infants from 0 to 6 months of age. Design: Forty-four full-term healthy neonates (17 males and 27 females) participated in a longitudinal study. The neonates were assessed at 1-month intervals from 0 to 6 months of age using high-frequency tympanometry, acoustic stapedial reflex, distortion product otoacoustic emissions, and pressurized WBA. The values of WBA at tympanometric peak pressure (TPP) and 0 daPa across the frequencies from 0.25 to 8 kHz were analyzed as a function of age. Results: A linear mixed model analysis, applied to the data, revealed significantly different WBA patterns among the age groups. In general, WBA measured at TPP and 0 daPa decreased at low frequencies (

from #Audiology via ola Kala on Inoreader https://ift.tt/2ICMz8F

Benefit of Higher Maximum Force Output on Listening Effort in Bone-Anchored Hearing System Users: A Pupillometry Study

Objectives: The aim of this study was to compare listening effort, as estimated via pupillary response, during a speech-in-noise test in bone-anchored hearing system (BAHS) users wearing three different sound processors. The three processors, Ponto Pro (PP), Ponto 3 (P3), and Ponto 3 SuperPower (P3SP), differ in terms of maximum force output (MFO) and MFO algorithm. The hypothesis was that listeners would allocate lower listening effort with the P3SP than with the PP, as a consequence of a higher MFO and, hence, fewer saturation artifacts in the signal. Design: Pupil dilations were recorded in 21 BAHS users with a conductive or mixed hearing loss, during a speech-in-noise test performed at positive signal-to-noise ratios (SNRs), where the speech and noise levels were individually adjusted to lead to 95% correct intelligibility with the PP. The listeners had to listen to a sentence in noise, retain it for 3 seconds and then repeat it, while an eye-tracking camera recorded their pupil dilation. The three sound processors were tested in random order with a single-blinded experimental design. Two conditions were performed at the same SNR: Condition 1, where the speech level was designed to saturate the PP but not the P3SP, and condition 2, where the overall sound level was decreased relative to condition 1 to reduce saturation artifacts. Results: The P3SP led to higher speech intelligibility than the PP in both conditions, while the performance with the P3 did not differ from the performance with the PP and the P3SP. Pupil dilations were analyzed in terms of both peak pupil dilation (PPD) and overall pupil dilation via growth curve analysis (GCA). In condition 1, a significantly lower PPD, indicating a decrease in listening effort, was obtained with the P3SP relative to the PP. The PPD obtained with the P3 did not differ from the PPD obtained with the other two sound processors. In condition 2, no difference in PPD was observed across the three processors. The GCA revealed that the overall pupil dilation was significantly lower, in both conditions, with both the P3SP and the P3 relative to the PP, and, in condition 1, also with the P3SP relative to the P3. Conclusions: The overall effort to process a moderate to loud speech signal was significantly reduced by using a sound processor with a higher MFO (P3SP and P3), as a consequence of fewer saturation artifacts. These findings suggest that sound processors with a higher MFO may help BAHS users in their everyday listening scenarios, in particular in noisy environments, by improving sound quality and, thus, decreasing the amount of cognitive resources utilized to process incoming speech sounds. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal's Web site (www.ear-hearing.com). ACKNOWLEDGMENTS: The authors thank Matthew Winn for the helpful discussion of the results. This work was supported by Oticon Medical AB (Askim, Sweden). T. R., M. H., T. L., D. W., C. W., and P. M. designed the experiments; C. W. performed the experiments; F. B. and D. W. analyzed the data; F. B. wrote the article and provided the Supplementary Digital Content; all authors discussed the results and provided critical revision on the manuscript. The authors have no conflicts of interest to disclose. Received August 3, 2018; accepted December 18, 2018. Address for correspondence: Federica Bianchi, Oticon Medical AB, Kongebakken 9, Smørum, Denmark. E-mail: fedb@oticonmedical.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader https://ift.tt/2Te1mej

A Comparison of Electrical Stimulation Levels Across Ears for Children With Sequential Bilateral Cochlear Implants

Objectives: To compare threshold and comfortable levels between a first and second cochlear implant (CI) for children, and to consider if the degree of difference between CIs was related to the age at bilateral implantation or the time between implants. A secondary objective was to examine the changes in levels over time for each CI . Design: Fifty-seven participants were selected from the 146 children and young adults who received a first Nucleus CI as a child, and received a second implant at the Royal Victorian Eye and Ear Hospital between September 2003 and December 2011. Exclusion criteria included an older implant type, incomplete array insertion, incomplete data available, and a pulse width higher than the default. Using measurements from clinical sessions, the threshold levels, comfortable levels, and dynamic range of electrical stimulation were compared at three electrode array regions and at the "initial" (first 10 weeks), 2-year, and 5-year postoperative time points. The T-ratio and C-ratio for each array region and each time point were calculated by dividing each mean (n = 3 electrodes) level for the second implant by that for the first implant. Results: The T-ratio was generally not significantly different to one, indicating no differences in threshold levels between the second and first implants; however, threshold levels were lower for the second implant in the apical region at the initial time point, and there was a significant difference in threshold levels in the apical region for children with a Contour Advance array for the second implant and an older-style array (i.e., Contour) for the first implant. For each implant individually, there were no significant changes in threshold levels across time. The C-ratio was significantly

from #Audiology via ola Kala on Inoreader https://ift.tt/2IEbDwi

Different Associations between Auditory Function and Cognition Depending on Type of Auditory Function and Type of Cognition

Objectives: Previous studies strongly suggest that declines in auditory threshold can lead to impaired cognition. The aim of this study was to expand that picture by investigating how the relationships between age, auditory function, and cognitive function vary with the types of auditory and cognitive function considered. Design: Three auditory constructs (threshold, temporal-order identification, and gap detection) were modeled to have an effect on four cognitive constructs (episodic long-term memory, semantic long-term memory, working memory, and cognitive processing speed) together with age that could have an effect on both cognitive and auditory constructs. The model was evaluated with structural equation modeling of the data from 213 adults ranging in age from 18 to 86 years. Results: The model provided good a fit to the data. Regarding the auditory measures, temporal-order identification had the strongest effect on the cognitive functions, followed by weaker indirect effects for gap detection and nonsignificant effects for threshold. Regarding the cognitive measures, the association with audition was strongest for semantic long-term memory and working memory but weaker for episodic long-term memory and cognitive speed. Age had a very strong effect on threshold and cognitive speed, a moderate effect on temporal-order identification, episodic long-term memory, and working memory, a weak effect on gap detection, and nonsignificant, close to zero effect on semantic long-term memory. Conclusions: The result shows that auditory temporal-order function has the strongest effect on cognition, which has implications both for which auditory concepts to include in cognitive hearing science experiments and for practitioners. The fact that the total effect of age was different for different aspects of cognition and partly mediated via auditory concepts is also discussed. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal's Web site (www.ear-hearing.com). ACKNOWLEDGMENTS: This study was financed by an excellence grant [349-2007-8654] from the Swedish Research council; a grant [2012-1693] from The Swedish Research Council for Health, Working Life and Welfare (to J.R.) and a grant [R01 AG008293] from the National Institute on Aging (to L.H.). The authors have no conflicts of interest to disclose. Address for correspondence: Henrik Danielsson, Department of Behavioural Sciences and Learning, Linköping University, 581 83 Linköping, Sweden. Email: henrik.danielsson@liu.se Received December 14, 2016; accepted December 18, 2018. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

from #Audiology via ola Kala on Inoreader https://ift.tt/2Tm8YeA

The effect of luminance values of the edge between regions on figure-ground perception

Abstract

The present study examined whether luminance values of an edge between regions affect figure-ground perception. A dark-gray or light-gray region was presented on the left (or upper) or right (or lower) side of an edge. Observers reported which region was perceived as a figure. The results in the 0.2° edge width condition showed that dark-gray regions with low luminance edges were perceived as a figure significantly more often than dark-gray regions with high luminance edges. The edge luminance effect occurred, partly occurred, and did not occur when the edge widths were 0.2, 0.5, and 0.8° of visual angle, respectively. These results showed that luminance values of the edge between the regions affected figure-ground perception, and that regions with luminance values closer to that of the edge between the regions were perceived as a figure more often, but only when the edge width was narrow. The edge luminance effect occurred less often as the edge width was increased and would be  attributed to similarity grouping between edge and region.

https://ift.tt/2SuDmz0

Elevated circulating T cell subsets and cytokines expression in patients with rheumatoid arthritis

Abstract

Objective

This study aimed to assess the role of different subsets of circulating follicular helper T cells (Tfh), central memory (TCM), effector memory (TEM), Naïve T, chemokines, and cytokines in the pathogenesis of rheumatoid arthritis (RA).

Methods

Blood samples from RA patients (n = 44) and healthy controls (n = 37) were analyzed. The frequencies of circulating Tfh, TCM, TEM, and Naïve T cell subsets were enumerated, and the expression of co-stimulatory molecules, such as inducible co-stimulator (ICOS) and programmed death-1 (PD1), on these cells was evaluated by flow cytometry. The disease state in RA patients was assessed using the DAS28. Concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), and rheumatoid factor (RF) were measured. Cytokines and chemokines, such as IL-1β, TNF-α, IL-4, IL-6, IL-9, IL-17A, MCP-1, IL-10, IL-12p70, and IL-21, were measured by a cytometric beads array assay.

Results

The percentages of circulating PD1⁺ICOS⁺ Tfh, PD1⁺ICOS⁺ TEM, and PD1⁺ICOS⁺ TCM of PBMCs from RA patients were higher than those in healthy controls. Furthermore, expression of circulating PD1⁺ICOS⁺ Tfh, PD1⁺ICOS⁺ TEM, and PD1⁺ICOS⁺ TCM showed a positive correlation with DAS28. In addition, increased levels of IL-1β, IL-6, and MCP-1 were detected in the patients with RA compared to healthy controls.

Conclusions

Elevated circulating T cell subsets and cytokines expression profile were observed in RA patients. IL-6, MCP-1, and IL-1β were significantly increased in RA, and PD1⁺ICOS⁺ TEM, PD1⁺ICOS⁺ TCM, and PD1⁺ICOS⁺ Tfh cell subsets were positively correlated with disease activity DAS28. Therefore, PD1⁺ICOS⁺ TEM, PD1⁺ICOS⁺ TCM, and PD1⁺ICOS⁺ Tfh cells might serve an important role in the progression of RA.

https://ift.tt/2HagdjB

Familial oligodontia and regional odontodysplasia associated with a PAX9 initiation codon mutation

Abstract

Objective

Tooth agenesis is one of the most common craniofacial developmental anomalies. In hypodontia, one to five teeth are missing, whereas oligodontia refers to the absence of at least six teeth, excluding the third molars. Mutations in several genes including MSX1, PAX9, AXIN2, and WNT10A have been shown to cause non-syndromic tooth agenesis. Regional odontodysplasia (RO), also known as "ghost teeth," is a rare developmental anomaly of tooth formation affecting both dentitions. Some possible causes of RO have been suggested, yet the etiology remains unknown. Because the phenotypes of both oligodontia and RO co-occur in one Finnish family, the aim here was to investigate the genetic etiology of the two conditions.

Materials and methods

A mutation screening of the genes MSX1, PAX9, AXIN2, and WNT10A was performed for the family members of a RO patient and family history of oligodontia.

Results

An initiation codon mutation of the PAX9 gene was found in the proband and segregating with oligodontia in the family.

Conclusions

The etiology of regional odontodysplasia (RO) may be genetic and the same genes can be involved both in RO and tooth agenesis.

Clinical relevance

Our results give new insights into the etiology of regional odontodysplasia, yet further results are needed.

https://ift.tt/2Ntp6pv

“My husband says this: If you are alive, you can be someone…”: Facilitators and barriers to cervical cancer screening among women living with HIV in India

Abstract

Purpose

Women living with human immunodeficiency virus (WLWH) have a higher risk of cervical cancer than women without HIV. In addition, women in India experience a high burden of death from cervical cancer. This qualitative study evaluated individual and interpersonal factors influencing cervical cancer screening among WLWH in Surat, India.

Methods

In-depth interviews were conducted with 25 WLWH and 15 stakeholders in Surat, India. Data were analyzed using directed content analysis to identify individual and intrapersonal barriers and facilitators.

Results

WLWH lacked knowledge and reported being afraid of cervical cancer and cervical cancer screening but were interested in learning more about it. Interpersonal factors influencing cervical cancer screening included receipt or lack of instrumental and emotional family support, interactions with healthcare providers, and receipt or lack of information about cervical cancer and the Pap test from healthcare providers.

Conclusion

Widespread public education is necessary to increase awareness of cervical cancer and cervical cancer screening and to encourage family members to support women who wish to obtain screening. Patient- and provider-focused interventions may facilitate the process of providing cervical cancer care to WLWH who are obtaining care in busy public healthcare systems in India.

https://ift.tt/2GNz0BM

Biochemical profiles of two thermostable and organic solvent–tolerant esterases derived from a compost metagenome

Abstract

Owing to the functional versatility and potential applications in industry, interest in lipolytic enzymes tolerant to organic solvents is increasing. In this study, functional screening of a compost soil metagenome resulted in identification of two lipolytic genes, est1 and est2, encoding 270 and 389 amino acids, respectively. The two genes were heterologously expressed and characterized. Est1 and Est2 are thermostable enzymes with optimal enzyme activities at 80 and 70 °C, respectively. A second-order rotatable design, which allows establishing the relationship between multiple variables with the obtained responses, was used to explore the combined effects of temperature and pH on esterase stability. The response curve indicated that Est1, and particularly Est2, retained high stability within a broad range of temperature and pH values. Furthermore, the effects of organic solvents on Est1 and Est2 activities and stabilities were assessed. Notably, Est2 activity was significantly enhanced (two- to tenfold) in the presence of ethanol, methanol, isopropanol, and 1-propanol over a concentration range between 6 and 30% (v/v). For the short-term stability (2 h of incubation), Est2 exhibited high tolerance against 60% (v/v) of ethanol, methanol, isopropanol, DMSO, and acetone, while Est1 activity resisted these solvents only at lower concentrations (below 30%, v/v). Est2 also displayed high stability towards some water-immiscible organic solvents, such as ethyl acetate, diethyl ether, and toluene. With respect to long-term stability, Est2 retained most of its activity after 26 days of incubation in the presence of 30% (v/v) ethanol, methanol, isopropanol, DMSO, or acetone. All of these features indicate that Est1 and Est2 possess application potential.

https://ift.tt/2EcDkXu

Nutrient removal in an algal membrane photobioreactor: effects of wastewater composition and light/dark cycle

Abstract

Graesiella emersonii was cultivated in an osmotic membrane photobioreactor (OMPBR) for nutrients removal from synthetic wastewater in continuous mode. At 1.5 days of hydraulic retention time and under continuous illumination, the microalgae removed nitrogen (N) completely at influent NH₄⁺-N concentrations of 4–16 mg/L, with removal rates of 3.03–12.1 mg/L-day. Phosphorus (P) removal in the OMPBR was through biological assimilation as well as membrane rejection, but PO₄³⁻-P assimilation by microalgae could be improved at higher NH₄⁺-N concentrations. Microalgae biomass composition was affected by N/P ratio in wastewater, and a higher N/P ratio resulted in higher P accumulation in the biomass. The OMPBR accumulated about 0.35 g/L biomass after 12 days of operation under continuous illumination. However, OMPBR operation under 12 h light/12 h dark cycle lowered biomass productivity by 60%, which resulted in 20% decrease in NH₄⁺-N removal and nearly threefold increase in PO₄³⁻-P accumulation in the OMPBR. Prolonged dark phase also affected carbohydrate accumulation in biomass, although its effects on lipid and protein accumulation were negligible. The microalgae also exhibited high tendency to aggregate and settle, which could be attributed to reduction in cell surface charge and enrichment of soluble algal products in the OMPBR. Due to a relatively shorter operating period, membrane biofouling and salt accumulation did not influence the permeate flux significantly. These results improve the understanding of the effects of N/P ratio and light/dark cycle on biomass accumulation and nutrients removal in the OMPBR.

https://ift.tt/2XpKRuL

Artificial Intelligence as a Socratic Assistant for Moral Enhancement

Abstract

The moral enhancement of human beings is a constant theme in the history of humanity. Today, faced with the threats of a new, globalised world, concern over this matter is more pressing. For this reason, the use of biotechnology to make human beings more moral has been considered. However, this approach is dangerous and very controversial. The purpose of this article is to argue that the use of another new technology, AI, would be preferable to achieve this goal. Whilst several proposals have been made on how to use AI for moral enhancement, we present an alternative that we argue to be superior to other proposals that have been developed.

https://ift.tt/2StBE0F

Authors’ Reply to Tsivgoulis et al.: “Oral Disease-Modifying Treatments for Relapsing Multiple Sclerosis: A likelihood to Achieve No Evidence of Disease Activity or Harm Analysis”

https://ift.tt/2tE0T6A

Comment on: “Oral Disease-Modifying Treatments for Relapsing Multiple Sclerosis: A Likelihood to Achieve No Evidence of Disease Activity or Harm Analysis”

https://ift.tt/2H4FqLW

Gastric Bypass Surgery Improves the Skeletal Muscle Ceramide/S1P Ratio and Upregulates the AMPK/ SIRT1/ PGC-1α Pathway in Zucker Diabetic Fatty Rats

Abstract

Purpose

Roux-en-Y gastric bypass (RYGB) is associated with remission of type 2 diabetes. However, the cellular and molecular mechanisms remain unknown. We hypothesized that RYGB would increase peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (SIRT1), AMPK/pAMPK, and citrate synthase (CS) protein expression and decrease insulin resistance and these changes would be mediated by sphingolipids, including ceramides and the sphingolipid metabolite sphingosine-1 phosphate (S1P).

Materials and Methods

Male ZDF rats were randomized to RYGB (n = 7) or sham surgery (n = 7) and harvested after 28 days. Total tissue ceramide, ceramide subspecies (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1), and S1P were quantified in the white gastrocnemius muscle using LC-ESI-MS/MS after separation with HPLC. Total SIRT1, AMPK, PGC-1α, and CS protein expression were measured by Western blot.

Results

Body weight, fasting glucose, insulin, and HOMA-IR decreased significantly after RYGB compared with sham control. These changes were paralleled by lower total ceramide (483.7 ± 32.3 vs. 280.1 ± 38.8 nmol/g wwt), C18:0 ceramide subspecies (P < 0.05), higher S1P (0.83 ± 0.05 vs. 1.54 ± 0.21 nmol/g wwt, P < 0.05), and a lower ceramide/S1P ratio (P < 0.05) in the RYGB versus sham group. AMPK, pAMPK, SIRT1, PGC-1α, and CS protein expression was also higher after RYGB (P < 0.05). The ceramide/S1P ratio correlated with weight loss (r = 0.48, P = 0.08), insulin resistance (r = 0.61, P = 0.02), PGC-1α (r = − 0.51, P < 0.06), CS (r = − 0.63, P = 0.01), and SIRT1 (r = − 0.54, P < 0.04).

Conclusion

Our data demonstrate that sphingolipid balance, and increased AMPK, SIRT1, PGC-1α, and CS protein expression are part of the mechanism that contributes to the remission of diabetes after RYGB surgery.

https://ift.tt/2tDpacS

Neurosonological and cognitive screening for evaluation of systemic sclerosis patients

Abstract

Objective

Assessment of cerebrovascular hemodynamics, third ventricle diameter (as a proxy of brain atrophy) by transcranial sonography (TCS), and screening of cognitive performance by the Symbol Digit Modalities Test (SDMT) in systemic sclerosis (SSc) patients.

Methods

A total of 38 SSc patients recruited from the outpatient clinic of the Rheumatology Department, Kasr Alainy Hospital, Cairo University, and 51, age- and sex-matched, healthy controls were included in the study. TCS was used to assess the mean flow velocity (MFV), pulsatility index (PI) of the anterior, middle, and posterior cerebral arteries bilaterally, and to measure the third ventricle diameter as a proxy of brain atrophy. Cognitive impairment was screened using the SDMT. p values < 0.05 were considered statistically significant.

Results

There was no significant difference between SSc patients and controls regarding either PI or MFV of the anterior, middle, and posterior cerebral arteries; also, there was no difference regarding the third ventricle diameter; however, limited SSc patients showed a significant increase in the PI of PCA and MFV of ACA as compared with diffuse SSc patients (p = 0.005, 0.004). There was a significant difference between SSc patients and controls regarding the SDMT (p = 0.016).

Conclusion

There is an evidence of increased cerebral vascular tone and resistance in limited SSc patients compared with diffuse SSc subgroup, without evidence of cerebral atrophy, suggesting early cerebrovascular affection even in asymptomatic limited SSc patients. There was also an evidence of cognitive impairment in SSc patients.

https://ift.tt/2EyGAOe

Prevalence of frailty and its associated factors in patients with rheumatoid arthritis: a cross-sectional analysis

Abstract

Objectives

The aims of the present research were to assess the prevalence of frailty and its potential associated factors in a cohort of adult patients with rheumatoid arthritis (RA).

Methods

Consecutive RA patients and healthy controls were assessed according to the Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI), and classified as frail, pre-frail, or non-frail. Chi-square, analysis of variance (ANOVA), and multinomial logistic regression analyses were used to test the prognostic value of frailty for the outcomes of interest.

Results

Two hundred and ten consecutive RA patients (65.7% female, mean age 60.4 years) and 100 healthy controls (63% female, mean age 59.1 years) were included. According to SHARE-FI criteria, 35 RA patients (16.6%) were categorized as frail, 68 (32.4%) as pre-frail, and 107 (51%) as non-frail, while 8 control subjects were categorized as frail, (8%), 17 as pre-frail (17%), and 75 as non-frail (75%) (chi-squared 12.8; P = 0.0016). The results from logistic regression analysis revealed that age (odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.07–1.17; P < 0.0001), comorbidities (OR = 1.51, 95% CI = 1.01–2.27; P = 0.0446), and high disease activity (OR = 1.10, 95% CI = 1.04–1.16; P = 0.0006) were independently associated with frailty in RA.

Conclusions

Frailty or pre-frailty are common in RA. The SHARE-FI may be a useful tool for the screening of frailty in RA and may summarize the results of a comprehensive RA assessment providing a marker of deficits accumulation.

https://ift.tt/2VrNElz

Spatial distribution of Haemaphysalis species ticks and human Kyasanur Forest Disease cases along the Western Ghats of India, 2017–2018

Abstract

Kyasanur Forest Disease (KFD) is a viral haemorrhagic fever, transmitted to humans and other hosts by a tick vector of genus Haemaphysalis. It affects 400–500 people annually in the Western Ghats region of India through spring to summer season. To understand the species composition, distribution, and abundance of Haemaphysalis ticks in endemic taluks (sub-districts) of India, a surveillance for ticks was conducted between October 2017 and January 2018. In total 105 sites were selected based on grid sampling from five taluks representing five KFD endemic states in south India. A sum of 8373 ticks were collected by using standard flagging method. The study showed a wide distribution of host seeking tick species among the selected taluks, wherein Haemaphysalis spinigera was predominant in 3/5 taluks, Haemaphysalis bispinosa in 1/5 taluks, and both the species in 1/5 taluks. Further, the H. spinigera abundance was categorised and compared with the incidence of human cases during the same season. The grids with very high and high H. spinigera abundance had 70% of the 205 human cases reported. This method of tick surveillance could be efficiently used as a standard model for KFD transmission risk assessment and prediction of impending outbreaks.

https://ift.tt/2H1c9lk

Facile route to porous polyaniline@nanodiamond-graphene based nanohybrid structures for DC electrical conductivity retention and supercapacitor applications

Abstract

Herein, in this work we have developed macroporous nanocomposite of polyaniline (Pani) with nanodiamond (ND) and graphene (GN) by the combination of oxidative aniline polymerization and hydrothermal methodology to prepare the overall composite. Morphological features showed that the ND particles and Pani tubes have been well dispersed inside the GN, thereby forming structures with high porosity. The high conductivity of GN in addition to the high thermal stability of ND is expected to give highly stable conductive Pani-ND@GN composite. The electrical transport studies was done by DC electrical conductivity retention under aging experiments and the Pani-ND@GN nanocomposites showed high stability under ambient conditions. Three electrode assembly was used for the electrochemical supercapacitive characteristics i.e. the cyclic voltammetric (CV) curves and galvanostatic charge discharge (GCD) of Pani-ND@GN. The obtained nanocomposite delivered a high capacitance of 150.20 F/g at 2 A/g and high cyclic stability of 84% after continuous 1000 charge-discharge cycles.

https://ift.tt/2Tgm5hC

Cadmium Accumulation in Peruvian Cacao ( Theobroma cacao L.) and Opportunities for Mitigation

Abstract

Crops are the main source of toxic cadmium for humans due to uptake from naturally or anthropogenically polluted soils. Chronic Cd ingestion causes kidney, liver, and skeletal damage along with an increased risk of cancer. Cacao is known to accumulate Cd and may therefore be potentially harmful to human health. Consequently, cocoa production on intensely polluted soils should be avoided. Cocoa products from South America in particular often exceed the limits for Cd, but the factors that drive Cd uptake are as yet poorly studied. In this study, we measured Cd concentrations in defatted cocoa powder from unfermented seeds of 40 different trees on 20 farms in the Huánuco Region, Peru, and associated the Cd levels with the farms' soil, field management, and nearby vegetation diversity. The mean Cd concentration found in cocoa of the study region was 2.46 mg kg⁻¹ with a range of 0.2–12.56 mg kg⁻¹. The maximum content measured was an order of magnitude higher than the allowed limit of 1.5 mg kg⁻¹ and was the highest reported so far in the literature. Soil Cd content was the most relevant driver of Cd concentration in cacao. In addition, fertilizer use caused significantly higher Cd concentration in cocoa. Higher biodiversity of herbs was positively correlated with Cd contents in cocoa. The study shows that, apart from the known correlation of soil conditions with Cd accumulation in cacao seeds, changes in fertilization and plant composition may be promising measures to counteract Cd contamination in regions with high soil Cd content.

https://ift.tt/2tG5epY

Proteases from dengue, West Nile and Zika viruses as drug targets

Abstract

Proteases from flaviviruses have gained substantial interest as potential drug targets to combat infectious diseases caused by dengue, West Nile, Zika and related viruses. Despite nearly two decades of drug discovery campaigns, promising lead compounds for clinical trials have not yet been identified. The main challenges for successful lead compound development are associated with limited drug-likeness of inhibitors and structural ambiguity of the protease target. This brief review focuses on the available information on the structure of flavivirus proteases and their interactions with inhibitors and attempts to point the way forward for successful identification of future lead compounds.

https://ift.tt/2NwkLlh

Inclusion of children in the initial conversation about their cancer diagnosis: impact on parent experiences of the communication process

Abstract

Introduction

Including children in medical conversations is considered the standard of care for children with cancer. However, previous qualitative research has raised concerns about how the child's presence impacts the parent's communication experience. The current study examines the frequency and impact of child presence during a serious medical conversation on the parent's communication experience in pediatric oncology.

Methods

Three hundred sixty parents of children newly diagnosed with cancer completed questionnaires assessing the child's presence during the initial conversation with the oncologist about diagnosis and treatment and parental communication experiences. Primary oncologists completed a survey question about the child's prognosis.

Results

Sixty-one percent of children were present during the initial conversation, with lowest rates among children aged 3–6 (44%) and 7–12 (44%). Child presence was not associated with parents' reports that they received prognostic information (p = 0.20), high-quality information (p = 0.19), or high-quality communication about the child's cancer (p = 1.0).

Discussion

The parent's communication experience is not diminished by the choice to include the child. Given the bioethical imperative to include children in conversations about serious illness whenever possible, this concern should not be used to exclude children, but rather to give parents additional time of their own when needed to fully process decisions.

https://ift.tt/2ID5AIg

Privacy protection based on binary fingerprint compression

Abstract

This paper proposes a novel system to protect the fingerprint database based on compressed binary fingerprint images. In this system, the user can store private data with high capacity. First, the grayscale fingerprint image is transformed into a binary bitstream. Then, the binary bitstream is compressed using run-length encoding and Huffman encoding technique to create a sparse space to accommodate private data. Finally, the new image constructed by the obtained binary bitstream is encrypted with an encryption key. For fingerprint matching, it is only need to decrypt and decompress the encrypted image in the database to obtain the binary fingerprint image. When the matching is passed, the private data can be extracted to a user with data-embedding key. If the matching is failed, the private data cannot extracted for the purpose of privacy security. Even if a leakage of the encryption key occurs, this system can still protect the privacy data of the user due to the existence of the data-embedding key. Meanwhile, the encoding and decoding phases are real time, which guarantee the practicability of the proposed system.

https://ift.tt/2H8fy25

Enhancing behavioral change among lung cancer survivors participating in a lifestyle risk reduction intervention: a qualitative study

Abstract

Purpose

Early detection and improved treatment have increased lung cancer survival. Lung cancer survivors have more symptom distress and lower function compared with other cancer survivors; however, few interventions are available to improve health-related quality of life (HR-QOL). Lifestyle risk reduction interventions have improved HR-QOL in other cancer survivors. The purpose of this study was to explore lung cancer survivor perspectives on making behavioral changes in the context of a lifestyle risk reduction intervention.

Methods

Twenty-two lung cancer survivors participated in interviews after completing the Healthy Directions (HD) intervention. Interviews were audiotaped, transcribed, and analyzed using inductive content analysis. Demographic and clinical characteristics were gathered through a survey and analyzed using descriptive statistics.

Results

Five main themes were identified: (1) the diagnosis was a motivator for behavior change, (2) participants had to deal with disease consequences, (3) the coach provided guidance, (4) strategies for change were initiated, and (5) social support sustained behavioral changes. Other important subthemes were the coach helped interpret symptoms, which supported self-efficacy and goal setting, and survivors employed self-monitoring behaviors. Several participants found the recommended goals for physical activity were difficult and were discouraged if unable to attain the goal. Findings underscore the need for individualized prescriptions of physical activity, especially for sedentary survivors.

Conclusions

Lung cancer survivors described the benefits of coaching to enhance their engagement in behavioral change. Additional research is needed to validate the benefit of the HD intervention to improve HR-QOL among this vulnerable and understudied group of cancer survivors.

https://ift.tt/2TiDztF

Do haematological cancer patients get the information they need about their cancer and its treatment? Results of a cross-sectional survey

Abstract

Purpose

To explore the experiences of haematological cancer outpatients in obtaining information about their cancer and its treatment.

Methods

A cross-sectional survey of adult haematological cancer outpatients was conducted. Participants completed two pen-and-paper questionnaires: the first examined demographics and disease characteristics; the second, completed four weeks later, asked about the cancer information received. Participants indicated whether they received the information they needed about medical procedures and self-management, experiences regarding doctor-patient communication, and self-efficacy in seeking information and support. Where possible, items were derived from Australian psychosocial cancer care guidelines.

Results

Two hundred and ninety-three (84%) patients consented to participate, with 170 (58%) completing both questionnaires. Most participants reported receiving information in accordance with guidelines. Areas identified as requiring improvement included difficulty recalling information (28%); information overload (26%); insufficient opportunity to ask questions (23%); and insufficient information about managing anxiety related to medical procedures (20%).

Conclusion

While many haematological cancer patients report receiving adequate information, there is room for improvement. Implementation of evidence-based strategies, such as decision aids or audiotapes of the consultation, may help to improve information experiences.

Practice implications

A patient-centred approach to information provision is essential for ensuring information addresses the needs and preferences of the patient.

https://ift.tt/2ID5Kzm

The role of depression and emotion regulation on parenting stress in a sample of mothers with cancer

Abstract

Purpose

The aim of the current study was to investigate if and to what extent depression and emotional regulation strategies (namely, cognitive reappraisal and expressive suppression) might lead to parenting stress in a sample of mothers with cancer and in a sample of healthy mothers.

Methods

A sample of mothers with cancer (clinical group; n = 64) and a sample of healthy mothers (control group; n = 80) were administered self-report questionnaires investigating parenting stress (the parenting stress index), depressive symptoms (the Zung depression self-rating scale) and emotion regulation strategies (the emotion regulation questionnaire).

Results

Depressive levels represented the most significant predictor of maternal parenting stress in both groups (p < .001). In addition, cognitive reappraisal (p < .05) but not expressive suppression significantly predicted parenting stress exclusively in the group of mothers with cancer. Finally, cognitive reappraisal was negatively and significantly associated with time since cancer diagnosis to survey.

Conclusions

This study highlights that depressive levels and cognitive reappraisal may play a significant role in parenting stress. The systematic assessment of these variables in women with an oncological diagnosis might help mental health professionals to identify those mothers at risk of developing higher levels of parenting stress ensuring adequate support and preventing negative effects on the parent–child relationship.

https://ift.tt/2IRgIBB

Relationship between skeletal muscle function, body composition, and weight loss in patients with advanced pancreatic and gastrointestinal cancers

Abstract

Background

Muscle function and its correlation with body composition and weight loss have not been studied deeply in pancreas and gastrointestinal cancers. This research aims to determine the skeletal muscle function and its relationship with body compartments, significant weight loss, and performance status (ECOG) 0-2 in a population with advanced digestive cancers.

Methods

A cross-sectional study was designed to determine the relationship between muscular function, weight loss, and body composition. Patients with advanced digestive adenocarcinomas were evaluated. Muscle strength was examined by hand grip technique and body composition by bioimpedance analysis. Values of hemoglobin and albumin were measured in plasma.

Results

A sample of 81 patients was included. They had adenocarcinoma of stomach (n = 9), pancreas (n = 28), or colorectum (n = 44). With regard to skeletal muscle function, sub-maximal strength increased when percentage of weight loss decreased (p = 0.002) or when any of the following variables increased: skeletal muscle (p < 0.001), waist-hip ratio (p < 0.001), body surface area (p < 0.001), and body mass index (p = 0.001). According to multivariate analysis of these variables, only percentage of weight loss and skeletal muscle remained statistically significant. Endurance had no correlation with any of the variables. Higher weight loss was found in tumors of the upper tract (stomach and pancreas) in comparison with those of the lower tract (colorectal) (p = 0.005).

Conclusions

In advanced digestive cancer, sub-maximal strength correlated inversely with weight loss and directly with skeletal muscle such as in lung and head and neck cancers. On the other hand, endurance had no correlation with any of the variables considered.

https://ift.tt/2Ey6i5i

Febrile neutropenia (FN) and pegfilgrastim prophylaxis in breast cancer and non-Hodgkin’s lymphoma patients receiving high (> 20%) FN-risk chemotherapy: results from a prospective observational study

Abstract

Purpose

Prophylaxis for febrile neutropenia (FN) is recommended for the duration of myelosuppressive chemotherapy in high-risk patients; yet, granulocyte-colony-stimulating factor (G-CSF) discontinuation occurs frequently in clinical practice. The objective of this study was to investigate the incidence of FN in real-world settings and the extent and impact of early pegfilgrastim discontinuation.

Methods

This prospective, observational study enrolled patients with any-stage non-Hodgkin's lymphoma (NHL) or breast cancer initiating a new chemotherapy course with a high (> 20%) FN risk, with pegfilgrastim in cycle 1. During routine clinical visits, data were collected on FN events, discontinuation of pegfilgrastim (defined as administration of G-CSF other than pegfilgrastim for ≥ 1 cycle) and all G-CSF (and reasons), neutropenic complications and adverse drug reactions (ADRs).

Results

Overall, 943 patients were enrolled; 844 met the eligibility criteria (full analysis set) and 814 (86%) completed the study. Twenty-eight patients (3%) had 31 FN events (NHL, n = 17; breast cancer, n = 11). Twenty-six patients (3%) discontinued pegfilgrastim. Forty-four patients (5%) discontinued G-CSF. The most common reason for pegfilgrastim discontinuation was physician preference for daily G-CSF (n = 14 [2%]), and for discontinuation of all G-CSFs was reduced FN risk (n = 14 [2%]). Patients who continued G-CSF prophylaxis were less likely to experience neutropenic complications (odds ratio [95% confidence interval]: 0.26 [0.09–0.80]). Suspected ADRs to pegfilgrastim occurred in 43 patients (5%) and serious ADRs in 5 (1%).

Conclusions

FN rates were consistent with previous reports with pegfilgrastim in clinical practice. No new ADRs were observed. G-CSF discontinuation was uncommon but appeared to increase the likelihood of neutropenic complications.

https://ift.tt/2Vnozb5

The prognostic and predictive role of hyponatremia in patients with advanced non-small cell lung cancer (NSCLC) with bone metastases

Abstract

Purpose

Hyponatremia and bone metastasis (BMs) are known as negative prognostic factors in patients affected by metastatic non-small cell lung cancer (NSCLC). Hyponatremia is associated with higher risk of osteoporosis and bone fracture, but no data are available about the relationship between hyponatremia and bone metastasis. This study aims to analyze the prognostic impact of hyponatremia in NSCLC patients with bone metastases.

Methods

We retrospectively collected data about advanced NSCLC patients. Survival curves were estimated using Kaplan–Meier method, and comparisons were made using chi-square test.

Results

Six hundred forty-seven patients were enrolled into the study. BMs were present in 264 patients (41%) at diagnosis, while hyponatremia appeared in 237 (37%) patients during the first-line treatment. Patients without BMs had a median overall survival (mOS) of 15.9 months (95% CI 14.1–17.9) versus 11.4 months (95% CI 9.4–13.4) for patients with BMs (p = 0.001). Eunatremic patients had a better outcome (mOS 16.3 months, 95% CI 14.6–18.0 vs 10.3 months, 95% I 7.6–12.8, p = 0.003). Considering the two variables, patients with BMs and hyponatremia had a mOS of 10.1 months (95% CI 4.3–15.9), patients with hyponatremia without BMs 11.9 months (95% CI 11.4–12.4), while mOS was 13.1 months (95% CI 12.0–14.2) for eunatremic patients with BMs versus 17.1 months (95% CI 15.2–19.1) in eunatremic patients without BMs (p = 0.0020). Hyponatremic patients developed metachronous BMs significantly earlier (3.73 vs 5.76 months, p = 0.0187).

Conclusions

Our study showed that hyponatremia is an important prognostic factor and it should be necessarily considered to enhance the management of NSCLC patients with BMs.

https://ift.tt/2EzbFRW

Urine cultures at the onset of febrile neutropenia rarely impact antibiotic management in asymptomatic adult cancer patients

Abstract

Purpose

There is a paucity of data regarding the utility of routine urine cultures in adults with febrile neutropenia (FN) without urinary symptoms receiving protocolised antibiotics. This is reflected by inconsistent recommendations in international and regional FN guidelines. We addressed this issue by retrospectively reviewing the impact of routine urine cultures on antibiotic management in haematology cancer inpatients at a tertiary hospital.

Methods

All haematology inpatients over a 5-year period (2011–2015) were retrospectively reviewed for episodes of FN (neutrophil count < 0.5 × 10⁹/L and fever > 37.5 °C). For each episode, demographic data, urinary tract symptoms and signs (absence of which was termed 'asymptomatic'), urinalysis and urine culture results, antibiotic therapy and duration, and patient outcomes were collected. A urine culture was considered positive if > 10⁵ colony forming units (CFU)/L were detected. Empiric antibiotic therapy for FN consisted of intravenous piperacillin/tazobactam in stable patients, with the addition of vancomycin and a single dose of gentamicin if systemically compromised.

Results

Four hundred and thirty-three episodes of FN were identified in 317 patients. Urine cultures were performed in 362 (84%) episodes. Cultures were positive in 9 of 48 (19%) symptomatic episodes versus 8 of 314 (2.5%) asymptomatic episodes (RR = 7.4, p < 0.0001). A change in antibiotic management due a positive urine culture occurred in only 5 episodes (1.4%): 3 of 48 (6.3%) symptomatic and 2 of 314 (0.6%) asymptomatic episodes respectively (RR = 9.8, p = 0.01).

Conclusion

Routine urine cultures in FN patients without urinary symptoms who are already receiving protocolised broad spectrum antibiotics rarely impact subsequent antibiotic management.

https://ift.tt/2ViHZhq

Correction to: Influence of cancer and acute inflammatory disease on taste perception: a clinical pilot study

The "Acknowledgment Statement" of the published paper is incorrect. The correct statement should be the below: Acknowledgements We thank Sarah Vogel for her support in taste test realization and Yvonne Sauermann for preparation of the tastant solutions. The present work was carried out by Ms. Schalk in order to meet the requirements for the awarding of the title of Dr. med. at the FAU.

https://ift.tt/2ExQrUB

Unmet supportive care needs in Hispanic/Latino cancer survivors: prevalence and associations with patient-provider communication, satisfaction with cancer care, and symptom burden

Abstract

Purpose

The aim of this study was to elucidate the prevalence of unmet supportive care needs in Hispanic/Latino cancer survivors and examine the association between unmet needs and patient-provider communication, satisfaction with cancer care, and cancer-specific symptom burden.

Methods

Hispanics/Latinos diagnosed with breast, prostate, or colorectal cancer within 15 months of treatment completion (n = 288) completed questionnaires as part of an NCI-funded project.

Results

Hispanic/Latino cancer survivors reported greater unmet needs compared to previously published norms in primarily non-Hispanic/Latino white samples. Across the three cancer types, the two most common unmet needs were in the psychological domain: fear of metastasis (32.6%) and concern for close others (31.3%). However, unmet needs varied by cancer type. Factors associated with greater unmet needs included more recent cancer diagnosis (OR .98 [.96–.99]), younger age (OR .96–.97 [.93–.99]), female gender (OR 2.53–3.75 [1.53–7.36]), and being single (OR 1.82 [1.11–2.97]). Breast cancer survivors reported greater unmet needs than both prostate and colorectal cancer survivors (OR 2.33–5.86 [1.27–14.01]). Adjusting for sociodemographic and medical covariates, unmet needs were associated with lower patient-provider communication self-efficacy (B = − .18–− .22, p's < .01) and satisfaction with cancer care (B = − 3.57–− 3.81, p's < .05), and greater breast (B = − 4.18–− 8.30, p's < .01) and prostate (B = − 6.01–− 8.13, p's < .01) cancer-specific symptom burden.

Conclusions

Findings document unmet supportive care needs in Hispanic/Latino cancer survivors and suggest that reducing unmet needs in Hispanic/Latino cancer survivors may improve not only satisfaction with care, but also health-related quality of life.

https://ift.tt/2TiDB4L

What determines the timing of discussions on forgoing anticancer treatment? A national survey of medical oncologists

Abstract

Purpose

End-of-life discussions (EOLd) including the option of forgoing anticancer treatment infrequently occur until treatment options have been exhausted for advanced cancer patients. We aimed to identify oncologist-related factors contributing to the timing of discussing the option of forgoing anticancer treatment.

Methods

In this nationwide survey of 864 medical oncologists, we asked about physicians' attitudes toward the timing of discussing the option of forgoing anticancer treatment for a simulated patient with newly diagnosed metastatic cancer, physicians' experience of EOLd, perceptions of a good death, and beliefs. Multivariate analyses identified determinants of early discussions.

Results

Among 490 physicians (response rate = 57%), 167 (35%) would discuss the option of forgoing anticancer treatment "now (at the diagnosis)." Physicians' attitudes toward discussing the option "now" were significantly correlated with a greater physician-perceived importance of life completion (odds ratio (OR) = 1.30, 95%CI = 1.00–1.69, p = 0.048) and dying in a preferred place (OR = 1.29, 95%CI = 1.01–1.65, p = 0.045) for a good death, and not perceiving EOLd as being severely distressing for patients/families (OR = 0.70, 95%CI = 0.54–0.95, p = 0.021). In multivariate analyses, independent determinants of the attitude toward discussing the option now included a greater physician-perceived importance of life completion for a good death (OR = 1.38, 95%CI = 1.05–1.81, p = 0.019), and not perceiving EOLd as being severely distressing for patients/families (OR = 0.70, 95%CI = 0.52–0.94, p = 0.017).

Conclusions

Reflection by oncologists on their own perception regarding a good death and beliefs about EOLd may help oncologists individualize the timing of discussing the option of forgoing anticancer treatment.

https://ift.tt/2VpjY8D

Frailty assessment prior to thoracic surgery for lung or esophageal cancer: a feasibility study

Abstract

Background

Frailty assessment has not been thoroughly assessed in thoracic surgery. Our primary objective was to assess the feasibility of comprehensive frailty testing prior to lung and esophageal surgery for cancer. The secondary objective was to assess the utility of frailty indices in risk assessment prior to thoracic surgery.

Methods

Prospectively recruited patients completed multiple physiotherapy tests (6-min walk, gait speed, hand-grip strength), risk stratification (Charlson Comorbidity Index, Revised Cardiac Risk Index, Modified Frailty Index), and quality of life questionnaires. Lean psoas area was also assessed by a radiologist using positron emission tomography/computed tomography scans. Data was analyzed using Fisher's exact, Mann-Whitney U and independent t tests.

Results

The feasibility of comprehensive frailty assessment was assessed over a 4-month period among 40 patients (esophagus n = 20; lung n = 20). Risk stratification questionnaires administered in clinic had 100% completion rates. Physiotherapy testing required a trained physiotherapist and an additional visit to the pre-admission clinic; these tests proved difficult to coordinate and had lower completion rates (63–75%). Although most measures were not significantly associated with occurrence of complications, the Modified Frailty Index approached statistical significance (p = 0.06).

Conclusions

Frailty assessment is feasible in the pre-operative outpatient setting and had a high degree of acceptance among surgeons and patients. Of the risk stratification questionnaires, the Modified Frailty Index may be useful in predicting outcomes as per this feasibility study. Pre-operative frailty assessment can identify vulnerable oncology patients to aid in treatment planning with the goal of optimizing clinical outcomes and resource allocation.

https://ift.tt/2TiDtCj

Pre-to-post diagnosis weight trajectories in colorectal cancer patients with non-metastatic disease

Abstract

Purpose

Previous studies have shown that > 50% of colorectal cancer (CRC) patients treated with adjuvant chemotherapy gain weight after diagnosis. This may affect long-term health. Therefore, prevention of weight gain has been incorporated in oncological guidelines for CRC with a focus on patients that undergo adjuvant chemotherapy treatment. It is, however, unknown how changes in weight after diagnosis relate to weight before diagnosis and whether weight changes from pre-to-post diagnosis are restricted to chemotherapy treatment. We therefore examined pre-to-post diagnosis weight trajectories and compared them between those treated with and without adjuvant chemotherapy.

Methods

We included 1184 patients diagnosed with stages I–III CRC between 2010 and 2015 from an ongoing observational prospective study. At diagnosis, patients reported current weight and usual weight 2 years before diagnosis. In the 2 years following diagnosis, weight was self-reported repeatedly. We used linear mixed models to analyse weight trajectories.

Results

Mean pre-to-post diagnosis weight change was −0.8 (95% CI −1.1, −0.4) kg. Post-diagnosis weight gain was + 3.5 (95% CI 2.7, 4.3) kg in patients who had lost ≥ 5% weight before diagnosis, while on average clinically relevant weight gain after diagnosis was absent in the groups without pre-diagnosis weight loss. Pre-to-post diagnosis weight change was similar in patients treated with (−0.1 kg (95%CI −0.8, 0.6)) and without adjuvant chemotherapy (−0.9 kg (95%CI −1.4, −0.5)).

Conclusions

Overall, hardly any pre-to-post diagnosis weight change was observed among CRC patients, because post-diagnosis weight gain was mainly observed in patients who lost weight before diagnosis. This was observed independent of treatment with adjuvant chemotherapy.

https://ift.tt/2EzbA0A